Surgical safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy: a systematic review and meta-analysis

Highlights • Bilateral Axillo-Breast Approach Robotic Thyroidectomy (BABART) has been developed.• We directly compare BABART with other approaches in outcomes and complications.• BABART's operation time, drainage, and cosmetic satisfaction were insufficient.• However, the surgical performance of BABART was not inferior.


Introduction
According to literature, thyroid surgery was performed using a knife for the first time in 1646, but the mortality rate was high. 1 Theodor Kocher reported that the mortality rate after thyroid surgery was reduced to 0.2% in 1898, and conventional Open Thyroidectomy (OT) also made many advances in reducing complications. 1 However, scars in the middle of the neck can create cosmetic disadvantages and patient discomfort. 2 To avoid an incision in the middle of the neck, an endoscopic approach was first introduced in 1996. 3Since then, the endoscopic approach has been widely used to remove thyroid tumors.The endoscopic approach is highly dependent on surgeon skill, and the lack of flexibility of the two-dimensional operating screen and instruments can limit thyroid tumor removal. 4,5However, a three-dimensional, expandable surgical field of view and the use of flexible surgical instruments for robotic thyroidectomy improved perioperative and operative outcomes and overcame the limitations of an endoscopic approach. 6ransaxillary and Bilateral Axillo-Breast Approach Robotic Thyroidectomy (BABART) techniques are widely used. 7ABART was first introduced in 2008. 8BABART has been compared with the bilateral axillo-breast approach endoscopic thyroidectomy (BABAET) 9 and to conventional OT. 10---12 However, evidence of the surgical safety and completeness of BABART is insufficient.
On the other hand, Transoral Robotic Thyroidectomy (TORT) requires less extensive dissection to create working space compared to BABART.The oral mucosal incision site of TORT can result in better healing. 13However, the effectiveness of TORT in comparison with BABART has yet to be fully evaluated. 14herefore, the purpose of our meta-analysis is to evaluate the safety and effectiveness of BABART by comparing it with TORT, conventional OT, and BABAET in terms of surgical completeness, perioperative outcomes, and postoperative complications.To the best of our knowledge, this is the first meta-analysis to directly compare BABART to other approaches.

Search strategy
We searched for and collected papers published before October 2023 from PubMed, SCOPUS, Embase, Web of Science, Google Scholar, and Cochrane databases.Retrospective or prospective studies written only in English were included.''Thyroidectomy, transoral thyroidectomy, remote-access thyroid surgery, minimally invasive surgery, robotic thyroidectomy, robotic thyroid surgery, surgical approaches, bilateral axillo-breast approach thyroidectomy, bilateral axillo-breast approach, open thyroidectomy, thyroid neoplasm, thyroid carcinoma, thyroid nodule, cosmesis, and comparison'' were used as the search terms.Among the searched studies, the two authors excluded those that did not mention BABART in the title and abstract.The selected studies were determined for inclusion in the meta-analysis by full text reading.A flow-chart for selecting eligible studies is summarized in Fig. 1.We registered the study protocol in the Open Science Framework (https://osf.io/kz9se/).This study was conducted with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2020 statement.

Data extraction and risk of bias assessment
From the included studies, number of patients, drainage amount, cosmetic satisfaction scores, operation time, days of hospitalization after operation, postoperative pain scores, retrieved Lymph Node (LN) number, postoperative thyroglobulin level, chyle leakage, incidental parathyroidectomy, postoperative infection, postoperative bleeding, transient or permanent postoperative hypoparathyroidism, transient or permanent Vocal Cord Palsy (VCP), and seroma were extracted.The data of the BABART group and other treatment group (conventional OT, BABAET, and TORT) were compared, and the p-values were extracted. 6,11,12,14---32The data were organized in a standardized format. 33,34The Newcastle-Ottawa Scale was used to evaluate non-randomized control studies. 35

Statistical analysis
We performed meta-analysis using 'R' statistical software (R Foundation for Statistical Computing, Vienna, Austria).When the original data were continuous, Mean Difference (MD) or Standard Mean Difference (SMD) were used for comparative analysis.For non-continuous variables, comparative analysis was performed using Odds Ratio (OR).In addition, we performed a sensitivity analysis to account for the impact of the included studies.

Results
We analyzed data from 8830 patients included in 22 studies.The characteristics of each study are summarized in Table 1.In Fig. 2, Egger's test and Begg's funnel plot analysis confirmed that there was no publication bias in the included studies as follows: operation time (0.1032), hospitalization (0.3126), retrieved LN number (0.1302), postoperative thyroglobulin level (0.5011) or incidence of permanent hypoparathyroidism (0.1121), permanent VCP (0.5193), and transient hypoparathyroidism (0.2093).However, the extraction results for drainage amount; cosmetic satisfaction; postoperative pain score; and incidence of chyle leak, hematoma, infection, and incidental parathyroidectomy were insufficient to perform a funnel plot or advanced regression-based assessment.Therefore, publication bias could not be assessed.Transient VCP suggested the possibility of bias from the results of Egger's test and Begg's funnel plot (p < 0.001).Duval and Tweedie's trim and fill results confirmed no significant difference between the observed and adjusted values (0.8069 [0.6474; 1.0057] vs. 0.79007 [0.5917; 1.001]).Therefore, the studies included in this meta-analysis can be stated to be unbiased in nature.= 98%) (Fig. 3).

Comparison of operation and postoperative course-related measurements according to operation type
Compared to conventional OT, the BABART group showed longer operative time (MD = 77.1700[33.5309; 120.8092], p < 0.0001), and greater patient cosmetic satisfaction (SMD = 4.0379 [0.0085; 8.0672], p = 0.0016) with statistical significance.There were no significant differences in other operation-related measurements between the two groups (Table 2).
There were no significant differences in other postoperative morbidities between BABART group and other approaches (Table 3).

Sensitivity analyses
Sensitivity analyses were performed to determine differences in integrated estimates in such a way that the meta-analysis was repeated excluding one study each time.All results were consistent with those above.

Discussion
Bilateral axillo-breast approach on thyroid can provide surgeons a symmetric surgical view of the thyroid through a midline approach as in conventional OT but with the largest operating angle for surgical instruments. 36In addition, good cosmetic satisfaction of patients can be expected due to the smaller wounds. 36Therefore, BABART has been evaluated as safe and effective for thyroid surgery. 37,38However, metaanalysis on the most recent data directly comparing BABART with other approaches remains insufficient.
In our study, BABART was not inferior to other thyroidectomy approaches in many respects but was inferior to TORT and BABAET in drainage amount.More extensive dissection is  required to obtain the necessary operation fields in BABART, resulting in a significantly larger drainage amount.A previous study showed that the cumulative drainage volume of BABART was larger than that of conventional OT. 15 For dissection time, BABART produced significantly longer operation times than the conventional OT in our study.This discrepancy from previous studies is potentially due to the extended time for flap dissection and docking of robotic instruments in BABART. 20,24,39If the surgeon's experience with BABART increases, the operation time may decrease, but the difference from OT operation time may not decrease significantly. 36However, an increase in the number of robotic surgeries may help overcome longer operation times. 39owever, hospitalization and postoperative pain scores did not significantly differ between other approaches and BABART.BABART reported decreased hospitalization period compared to BABAET.The average length of hospitalization after BABART was 3---5 days, and there was no significant difference between conventional OT and the length of stay in previous reports. 19,20The postoperative pain scores were different in each previous study, 12,21 but BABART was reported to be at least equivalent to conventional OT. 36 In addition, the cosmetic satisfaction score of BABART was significantly higher than that of conventional OT but significantly lower than that of TORT.Even though the measurement scale for cosmetic satisfaction was different in previous studies, the cosmetic satisfaction of BABART was significantly higher compared to conventional OT. 19,20,40 TORT has better cosmetic outcomes than BABART because wounds in the oral mucosa heal well and are not readily visible. 14or operative outcomes, retrieved LN number and postoperative thyroglobulin level were not significantly dif-ferent between other approaches and BABART.However, in the BABART group, retrieved LN number was significantly greater and postoperative thyroglobulin level was significantly lower than those of BABAET.The appropriateness of oncologic control can be based on the retrieved LN number from central node dissection. 36Retrieved central LN number previously was significantly lower with BABART compared to OT, 21 but there was no significant difference in our results.BABAET may have limitations in central LN number because the instruments are linear and access to the peritracheal area or upper mediastinum is limited. 14A robotic system was recommended to solve this limitation of BABAET, 27 and our results potentially support this recommendation.
The surgical completeness of thyroidectomy can be evaluated through serum thyroglobulin level and total dose of radioactive iodine. 41The thyroglobulin level is an index that can determine the degree of remnant thyroid; a previous study showed no significant difference between BABART and OT. 39Choi et al. reported that the recurrence rate of thyroid malignancy was lower in BABART compared to BABAET. 6egarding postoperative complications, BABART exhibited significantly better results in VCP or hypoparathyroidism than conventional OT or BABAET group.Other complications showed no significant difference between BABART and other approaches.Therefore, BABART did not appear to cause any additional risk compared to other approaches in terms of postoperative complications, especially in hypoparathyroidism and VCP.
This study has several limitations.First, included studies were mostly retrospective and randomized controlled trials, potentially creating selection bias.The subjects or conditions of included RCT may not be consistent.In addition, there may be publication bias or selection bias in the RCT itself.Second, the complication rate was not high in most studies, making it difficult to identify the exact difference.Third, complications such as chest numbness after BABART were not evaluated.Fourth, different evaluation scales for postoperative pain or cosmetic satisfaction may increase heterogeneity.Fifth, heterogeneity may be increased because postoperative management (pain control, wound care, or postoperative dieting) and instruments used for surgery differ by institution and surgeon's skill level or experience.

Conclusion
BABART was inferior to TORT in drainage and cosmetic satisfaction.However, in terms of surgical completeness and transient VCP, BABART was better than BABAET.BABART also showed better results in lower chance of transient hypoparathyroidism compared to BABAET and conventional OT.Since BABART had higher cosmetic satisfaction than conventional OT and did not report additional complications, an individualized appropriate approach for patients with thyroid tumors should be selected.

Figure 1
Figure 1 Diagram of study selection.

Figure 2
Figure 2 Funnel plot for publication bias of operation time (A), hospitalization (B), retrieved LN number (C), postoperative thyroglobulin level (D) or incidence of permanent hypoparathyroidism (E), permanent vocal cord palsy (F), transient hypoparathyroidism (G), and transient vocal cord palsy (H).

Table
The characteristics of the included studies.

Table 2
Comparison of operation-related measurements according to operation type.